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Objective: Little is known about the changing risk profile of death and conditional survival in patients with operable thyroid cancer. This study aimed to investigate the annual hazard rate of cancer death, actuarial disease-specific survival (DSS), and conditional DSS in patients with thyroid cancer and explore the effects of tumor differentiation. Methods: Patients diagnosed with thyroid cancer (N = 132,354) between 2004 and 2019 were identified from the Surveillance, Epidemiology, and End Results database. The hazard function was used to estimate the annual hazard rate of death. The Kaplan-Meier method and log-rank test were used for the calculation and between-group comparison of actuarial DSS, respectively. The life table was used to estimate the conditional DSS. Results: A total of 1896 (1.4%) patients died due to thyroid cancer during the follow-up period. Patients with ATC (68.9%, 313/454) were more likely to die than those with PDTC (19.4%, 171/883) or DTC (1.1%, 1412/131017). For the entire cohort, patients with DTC and PDTC had excellent and relatively stable one-year conditional survival, respectively; patients with ATC had the worst one-year conditional survival, but they achieved the greatest improvements. The worst one-year conditional survival and the most obvious improvement were seen in patients with ATC regardless of any SEER Summary Stage. Conclusion: Prognosis improved over time in a tumor differentiation-dependent manner in patients with operable thyroid cancer after diagnosis. This information provides more precise dynamic evaluations of the long-term prognosis of thyroid cancer survivors and paramount clinical implications for individualized treatment and surveillance. [ABSTRACT FROM AUTHOR]

Abstract Background In terms of survival rate, recurrent oral squamous cell carcinoma (OSCC) after primary surgery is considered as a poor prognostic indicator. Objective This study aims to determine the incidence of OSCC recurrence among patients treated at Khartoum Teaching Dental Hospital (KTDH) and possible risk factors associated with it. Methods Records of 303 patients with a history of radical surgery were retrieved from the hospital’s archives, and the histopathological records were retrieved from the archival specimens of Professor Ahmed Suleiman Oral Pathology Laboratory, Faculty of Dentistry, and University of Khartoum. Results Advanced stages of OSCC (III, IV) were associated with higher recurrence rates, and the poorly differentiated OSCC was the commonest recurrent type. Conclusion The condition of the surgical margin is a significant predictor of OSCC recurrence and tumor stage. The tumor site, the type of surgical resection, and the tumor differentiation were also identified as significant factors influencing the recurrence of OSCC.

This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease. [ABSTRACT FROM AUTHOR]

Background: In terms of survival rate, recurrent oral squamous cell carcinoma (OSCC) after primary surgery is considered as a poor prognostic indicator. Objective: This study aims to determine the incidence of OSCC recurrence among patients treated at Khartoum Teaching Dental Hospital (KTDH) and possible risk factors associated with it. Methods: Records of 303 patients with a history of radical surgery were retrieved from the hospital's archives, and the histopathological records were retrieved from the archival specimens of Professor Ahmed Suleiman Oral Pathology Laboratory, Faculty of Dentistry, and University of Khartoum. Results: Advanced stages of OSCC (III, IV) were associated with higher recurrence rates, and the poorly differentiated OSCC was the commonest recurrent type. Conclusion: The condition of the surgical margin is a significant predictor of OSCC recurrence and tumor stage. The tumor site, the type of surgical resection, and the tumor differentiation were also identified as significant factors influencing the recurrence of OSCC. [ABSTRACT FROM AUTHOR]

ObjectiveLittle is known about the changing risk profile of death and conditional survival in patients with operable thyroid cancer. This study aimed to investigate the annual hazard rate of cancer death, actuarial disease-specific survival (DSS), and conditional DSS in patients with thyroid cancer and explore the effects of tumor differentiation.MethodsPatients diagnosed with thyroid cancer (N = 132,354) between 2004 and 2019 were identified from the Surveillance, Epidemiology, and End Results database. The hazard function was used to estimate the annual hazard rate of death. The Kaplan-Meier method and log-rank test were used for the calculation and between-group comparison of actuarial DSS, respectively. The life table was used to estimate the conditional DSS.ResultsA total of 1896 (1.4%) patients died due to thyroid cancer during the follow-up period. Patients with ATC (68.9%, 313/454) were more likely to die than those with PDTC (19.4%, 171/883) or DTC (1.1%, 1412/131017). For the entire cohort, patients with DTC and PDTC had excellent and relatively stable one-year conditional survival, respectively; patients with ATC had the worst one-year conditional survival, but they achieved the greatest improvements. The worst one-year conditional survival and the most obvious improvement were seen in patients with ATC regardless of any SEER Summary Stage.ConclusionPrognosis improved over time in a tumor differentiation-dependent manner in patients with operable thyroid cancer after diagnosis. This information provides more precise dynamic evaluations of the long-term prognosis of thyroid cancer survivors and paramount clinical implications for individualized treatment and surveillance.

Purpose: To investigate the predictive factors of pathologic complete response (pCR) in locally advanced rectal cancer (LARC) patients who had been treated with neoadjuvant chemoradiation (nCRT). Methods and materials: For this retrospective study, 53 LARC patients (37 males and 16 females; age range 25 to 79 years) were selected. Clinical characteristics, baseline mrTNM staging, MR gross tumor volumes (GTV), and pCR were evaluated. The diagnostic accuracy of GTV for predicting pCR was calculated. Results: Among 53 LARC patients, 15 patients achieved pCR (28.3%), while 38 patients achieved non-pCR. Only three (5.7%) out of 53 patients did not downstage after nCRT. GTV and tumor differentiation were the significant prognostic parameters for predicting pCR. A tumor volume threshold of 21.1 cm3 was determined as a predictor for pCR, with a sensitivity of 84% and specificity of 47%. In addition, GTV was associated with mrN stage, circumferential resection margin (CRM) status, extramural vascular invasion (EMVI) status, and pretreatment serum CEA level. Conclusion: Tumor volume and tumor differentiation have significant predictive values in preoperative assessment of pCR among LARC patients. These findings aid clinicians to discriminate those patients who may likely benefit from preoperative regimens and to make optimal treatment plans. [ABSTRACT FROM AUTHOR]

Raman spectroscopy, a non-invasive diagnostic technique capturing molecular vibrations, offers significant advancements in skin cancer diagnostics. This review delineates the ascent of Raman spectroscopy from classical methodologies to the forefront of modern technology, emphasizing its precision in differentiating between malignant and benign skin tissues. Our study offers a detailed examination of distinct Raman spectroscopic signatures found in skin cancer, concentrating specifically on squamous cell carcinoma, basal cell carcinoma, and melanoma, across both in vitro and in vivo research. The discussion extends to future possibilities, spotlighting enhancements in portable Raman instruments, the adoption of machine learning for spectral data refinement, and the merging of Raman imaging with other diagnostic techniques. The review culminates by contemplating the broader implications of these advancements, suggesting a trajectory that may significantly optimize the accuracy and efficiency of skin cancer diagnostics. [ABSTRACT FROM AUTHOR]

Objective To detect the expression of lysosome-associated membrane protein 1(LAMP1) in colorectal cancer (CRC) and study the relationship between LAMP1 expression and important clinical and pathological indicators of CRC, especially disease prognosis. Methods The expression and prognostic characteristics of LAMP1 in CRC were retrieved through bioinformatics analysis at the big data level. qPCR and immunohistochemical (IHC) detection were performed on 10 clinical CRC tumor tissues and tissue chips containing 60 CRC samples. Univariate and multivariate Cox regression and Kaplan-Meier survival analysis were used to analyze the prognostic factors of CRC. Results Big data showed that LAMP1 protein was mainly located in lysosomes and had varying degrees of high expression in CRC cell lines, and was significantly higher in CRC tumor tissues than in normal control tissues. The recurrence free survival (RFS) and overall survival (OS) of CRC patients with high LAMP1 expression were lower than those with low LAMP1 expression. Both qPCR and IHC results of 10 clinical cases showed that the expression of LAMP1 in CRC was significantly higher than that in adjacent control tissues (P＜0.05). In the analysis of 60 cases of cohort, univariate Cox model analysis showed that LAMP1 expression (P=0.030), tumor differentiation (P=0.041), CEA level (P=0.028) and distant metastasis (P=0.002) were significantly correlated with the prognosis of CRC. Multivariate analysis showed that tumor differentiation (P=0.006) and distant metastasis (P=0.041) were independent prognostic factors; Survival analysis showed that the overall survival was shorter in patients with high expression of LAMP1, poor tumor differentiation, CEA level≥15 ng/mL and positive distant metastasis. Conclusion LAMP1 is abnormal highly expressed in CRC. LAMP1 expression is significantly correlated with CRC malignant phenotype, which may serve as a predictive indicator of CRC prognosis.

This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease.

Background: To evaluate the association between perfusion parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with prognostic factors in primary rectal cancer patients. Methods: A sample of 51 patients with pathologically proven rectal adenocarcinoma through surgery were retrospectively enrolled. All the patients underwent preoperative DCE-MRI including 3D-spoiled gradient echo. Two radiologists determined the tumor border after radiologic–pathologic correlation and drew regions of interest. The perfusion parameters, including the volume transfer constant (Ktrans), were calculated under the extended Toft model. The prognostic factors included TN stage, circumferential resection margin, extramural venous invasion, Kirsten-ras mutation, tumor size, carcinoembryonic antigen, and tumor differentiation. The association was assessed via correlation or t-test. For significant prognostic factors, receiver operating characteristic (ROC) curve analyses were performed to estimate the diagnostic predictive values. Results: Ktrans only showed a significant difference according to tumor differentiation, between the well-differentiated (n = 6) and moderately differentiated (n = 45) groups (0.127 ± 0.032, 0.084 ± 0.036, p = 0.036). The AUC was 0.838 (95% CI, 0.702–0.929), and the estimated accuracy, sensitivity, and specificity were 87%, 90%, and 60%, respectively. Conclusions: Ktrans showed a significant difference based on tumor differentiation, which may be conducive to prediction of prognosis in primary rectal cancer.

Background: To evaluate the association between perfusion parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with prognostic factors in primary rectal cancer patients. Methods: A sample of 51 patients with pathologically proven rectal adenocarcinoma through surgery were retrospectively enrolled. All the patients underwent preoperative DCE-MRI including 3D-spoiled gradient echo. Two radiologists determined the tumor border after radiologic–pathologic correlation and drew regions of interest. The perfusion parameters, including the volume transfer constant (Ktrans), were calculated under the extended Toft model. The prognostic factors included TN stage, circumferential resection margin, extramural venous invasion, Kirsten-ras mutation, tumor size, carcinoembryonic antigen, and tumor differentiation. The association was assessed via correlation or t-test. For significant prognostic factors, receiver operating characteristic (ROC) curve analyses were performed to estimate the diagnostic predictive values. Results: Ktrans only showed a significant difference according to tumor differentiation, between the well-differentiated (n = 6) and moderately differentiated (n = 45) groups (0.127 ± 0.032, 0.084 ± 0.036, p = 0.036). The AUC was 0.838 (95% CI, 0.702–0.929), and the estimated accuracy, sensitivity, and specificity were 87%, 90%, and 60%, respectively. Conclusions: Ktrans showed a significant difference based on tumor differentiation, which may be conducive to prediction of prognosis in primary rectal cancer. [ABSTRACT FROM AUTHOR]

Background. Numerous studies have shown circular RNA (circRNA) dysregulation is associated with the pathogenesis of cervical cancer, particularly in individual carcinoma variants. The aim of this study is to investigate and contrastively analyze the expression pattern of circRNAs in cervical squamous carcinoma and adenocarcinoma mediated by human papillomavirus type 16 (HPV-16). Methods. The expression of circRNAs in cervical squamous carcinoma (SCC), adeno-carcinoma (ADC) and adenosquamous carcinoma (ASC) tissues, together with the adjacent normal tissues (ANT), was profiled by high-throughput RNA sequencing (RNA-seq). Bioinformatics analysis and quantitative real time polymerase chain reaction (qRT-PCR) validation of the sequencing data were performed. A network of circRNA-miRNA (microRNA)-mRNA was then constructed according to predicted targets and function of candidate circRNAs. Results. A total of 11,685 annotated circRNAs were identified in six cervical samples. There were 42 up-regulated and 98 down-regulated circRNAs. 215 circRNAs were up-regulated in SCC but down-regulated circRNAs in ADC, while 50 circRNAs displayed the opposite trend. Function enrichment analysis based on different expressions of circRNAs found that the most enriched pathway in all the three pathologic variants of cervical cancer was the "ubiquitin mediated proteolysis" pathway. Eight key candidate circRNAs derived from this pathway were further validated, and we noticed that several target miRNAs of candidate circRNAs could target the source genes. Based on this we constructed a related competing endogenous RNA (ceRNA) network. Conclusion. Through a comprehensive interpretation of differentially expressed circRNAs in different pathologic variants of cervical cancer, this study provides new insights into the process of tumor differentiation mediated by HPV. Our results may help to complement the molecular typing and stem cell theory of cervical cancer. [ABSTRACT FROM AUTHOR]

Objective: Neuroblastoma (NB) is the most common extracranial solid tumor in children and is responsible for 12% of cancer-related deaths. The status of metastatic disease in the bone marrow (BM) is a predictor of poor outcome. The purpose of this study was to investigate the predictive significance of histopathological examination of BM in NB. Material and Method: The study included 61 cases with archival bone marrow biopsy tissues. The cases were evaluated regarding the percentage of metastatic tissue and its differentiation. Primary tumor slides were also reviewed to perform the Shimada classification based on the differentiation status and mitosis-karyorrhexis index. The patients' age, gender, NMYC amplification, clinical risk group, and disease outcome were also noted. Results: Of the 61 cases, 17 had BM involvement. Of those, eight cases (47.1%) were refractory NB showing disease relapse. Based on BM examination, five cases (29.4%) were categorized as complete response, seven (41.2%) as progressive disease, three (17.6%) as minimal disease, and two (11.8%) as stable disease. The progressive disease category was significantly related with refractory disease and NMYC amplification along with the high-risk category (p =0.002 and p= 0.003 respectively). Undifferentiated histology and presence of more than 20% of tumor tissue in the BM biopsy at diagnosis were significantly associated with the progressive disease category (p=0.01 and p

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma in which microenvironmental (niche) factors promote PDAC progression. In mouse models, reduction of the stroma increased the proportion of poorly differentiated PDAC with a worse prognosis. Here, we aimed to clarify the effects of stroma on PDAC that may define the PDAC phenotype and induce distinct therapeutic responses. Methods The molecular features of PDAC based on differentiation grade were clarified by genome and transcriptome analysis using PDAC organoids (PDOs). We identified the dependency on niche factors that might regulate the differentiation grade. A three-dimensional co-culture model with cancer-associated fibroblasts (CAFs) was generated to determine whether CAFs provide niche factors essential for differentiated PDAC. PDOs were subtyped based on niche factor dependency, and the therapeutic responses for each subtype were compared. Results The expression profiles of PDOs differed depending on the differentiation grade. Consistent with the distinct profiles, well differentiated types showed high niche dependency, while poorly differentiated types showed low niche dependency. The three-dimensional co-culture model revealed that well differentiated PDOs were strongly dependent on CAFs for growth, and moderately differentiated PDOs showed plasticity to change morphology depending on CAFs. Differentiated PDOs upregulated the expression of mevalonate pathway-related genes correlated with the niche dependency and were more sensitive to simvastatin than poorly differentiated PDOs. Conclusions Our findings suggest that CAFs maintain the differentiated PDAC phenotype through secreting niche factors and induce distinct drug responses. These results may lead to the development of novel subtype-based therapeutic strategies.

Purpose: To investigate if quantitative contrast enhancement and iodine mapping of common brain tumor (BT) entities may correctly differentiate between tumor etiologies in standardized stereotactic CT protocols. Material and Methods: A retrospective monocentric study of 139 consecutive standardized dual-layer dual-energy CT (dlDECT) scans conducted prior to the stereotactic needle biopsy of untreated primary brain tumor lesions. Attenuation of contrast-enhancing BT was derived from polyenergetic images as well as spectral iodine density maps (IDM) and their contrast-to-noise-ratios (CNR) were determined using ROI measures in contrast-enhancing BT and healthy contralateral white matter. The measures were correlated to histopathology regarding tumor entity, isocitrate dehydrogenase (IDH) and MGMT mutation status. Results: The cohort included 52 female and 76 male patients, mean age of 59.4 (±17.1) years. Brain lymphomas showed the highest attenuation (IDM CNR 3.28 ± 1,23), significantly higher than glioblastoma (2.37 ± 1.55, p < 0.005) and metastases (1.95 ± 1.14, p < 0.02), while the differences between glioblastomas and metastases were not significant. These strongly enhancing lesions differed from oligodendroglioma and astrocytoma (Grade II and III) that showed IDM CNR in the range of 1.22–1.27 (±0.45–0.82). Conventional attenuation measurements in DLCT data performed equally or slightly superior to iodine density measurements. Conclusion: Quantitative attenuation and iodine density measurements of contrast-enhancing brain tumors are feasible imaging biomarkers for the discrimination of cerebral tumor lesions but not specifically for single tumor entities. CNR based on simple HU measurements performed equally or slightly superior to iodine quantification. [ABSTRACT FROM AUTHOR]

This research introduces a novel method for evaluating the structural features of biomolecules, utilizing our innovative Elliptical Dichroism (ED) spectrometer specifically designed for stereochemical analysis. By integrating ED spectrometry with autocorrelation (AC) analysis, we investigate the conformational characteristics of biological molecules such as amino acids, proteins, and extracellular vesicles (EVs) induced by elliptically polarized UV absorption. Our streamlined approach offers a cost-effective and portable solution with minimal sample consumption and supports multiple working modes to efficiently characterize biomolecular structures. The insight from this new approach demonstrates potential applications in using biomolecular characterization for cancer detection., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Published by Elsevier Ltd.)

Abstract Methods We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). Results Between 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three‐level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5‐year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p

Pituitary adenomas (PAs) are the second most common primary brain tumor and may develop from any of the cell lineages responsible for producing the different pituitary hormones. DNA methylation is one of the essential epigenetic mechanisms in cancers, including PAs. In this study, we measured the expression profile and promoter methylation status of carbohydrate sulfotransferase 7 (CHST7) in patients with PA; then, we investigated the effect of the CHST7 methylation status on the proliferation and differentiation of PAs. The volcano map and Metascape results showed that the levels of CHST7 were related to the lineages' differentiation and the cell adhesion of PAs, and patients with low CHST7 had greater chances of having an SF-1 lineage (p = 0.002) and optic chiasm compression (p = 0.007). Reactome pathway analysis revealed that most of the DEGs involved in the regulation of TP53 regulated the transcription of cell cycle genes (HSA-6791312 and HSA6804116) in patients with high CHST7. Correlation analysis showed that CHST7 was significantly correlated with the eIF2/ATF4 pathway and mitochondrion-related genes. The AUC of ROC showed that CHST7 (0.288; 95% CI: 0.187–0.388) was superior to SF-1 (0.555; 95% CI: 0.440–0.671) and inferior to FSHB (0.804; 95% CI: 0.704–0.903) in forecasting the SF-1 lineage (p < 0.001). The SF-1 lineage showed a higher methylation frequency for CHST7 than the Pit-1 and TBX19 lineages (p = 0.009). Furthermore, as the key molecule of the hypothalamic–pituitary–gonadal axis, inhibin βE (INHBE) was positively correlated with the levels of CHST7 (r = 0.685, p < 0.001). In summary, CHST7 is a novel pituitary gland specific protein in SF-1 lineage adenomas with a potential role in gonadotroph cell proliferation and lineage differentiation in PAs. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). Methods: A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. Results: In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07–1.59), 1.07 (95% CI 0.89–1.28), 1.31 (95% CI 1.06–1.62), and 1.81 (95% CI 1.03–3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring

Abstract Purpose To compare integrated slice-specific dynamic shimming (iShim) diffusion weighted imaging (DWI) and single-shot echo-planar imaging (SS-EPI) DWI in image quality and pathological characterization of rectal cancer. Materials and methods A total of 193 consecutive rectal tumor patients were enrolled for retrospective analysis. Among them, 101 patients underwent iShim-DWI (b = 0, 800, and 1600 s/mm2) and 92 patients underwent SS-EPI-DWI (b = 0, and 1000 s/mm2). Qualitative analyses of both DWI techniques was performed by two independent readers; including adequate fat suppression, the presence of artifacts and image quality. Quantitative analysis was performed by calculating standard deviation (SD) of the gluteus maximus, signal intensity (SI) of lesion and residual normal rectal wall, apparent diffusion coefficient (ADC) values (generated by b values of 0, 800 and 1600 s/mm2 for iShim-DWI, and by b values of 0 and 1000 s/mm2 for SS-EPI-DWI) and image quality parameters, such as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of primary rectal tumor. For the primary rectal cancer, two pathological groups were divided according to pathological results: Group 1 (well-differentiated) and Group 2 (poorly differentiated). Statistical analyses were performed with p

Objective: Neuroblastoma (NB) is the most common extracranial solid tumor in children and is responsible for 12% of cancer-related deaths. The status of metastatic disease in the bone marrow (BM) is a predictor of poor outcome. The purpose of this study was to investigate the predictive significance of histopathological examination of BM in NB. Material and Method: The study included 61 cases with archival bone marrow biopsy tissues. The cases were evaluated regarding the percentage of metastatic tissue and its differentiation. Primary tumor slides were also reviewed to perform the Shimada classification based on the differentiation status and mitosis-karyorrhexis index. The patients' age, gender, NMYC amplification, clinical risk group, and disease outcome were also noted. Results: Of the 61 cases, 17 had BM involvement. Of those, eight cases (47.1%) were refractory NB showing disease relapse. Based on BM examination, five cases (29.4%) were categorized as complete response, seven (41.2%) as progressive disease, three (17.6%) as minimal disease, and two (11.8%) as stable disease. The progressive disease category was significantly related with refractory disease and NMYC amplification along with the high-risk category (p =0.002 and p= 0.003 respectively). Undifferentiated histology and presence of more than 20% of tumor tissue in the BM biopsy at diagnosis were significantly associated with the progressive disease category (p=0.01 and p<0.001, respectively). Conclusion: We conclude that evaluating the percentage of metastatic tumor tissue and tumor differentiation in BM biopsies is of clinical importance in the management of neuroblastoma patients. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma in which microenvironmental (niche) factors promote PDAC progression. In mouse models, reduction of the stroma increased the proportion of poorly differentiated PDAC with a worse prognosis. Here, we aimed to clarify the effects of stroma on PDAC that may define the PDAC phenotype and induce distinct therapeutic responses. Methods: The molecular features of PDAC based on differentiation grade were clarified by genome and transcriptome analysis using PDAC organoids (PDOs). We identified the dependency on niche factors that might regulate the differentiation grade. A three-dimensional co-culture model with cancer-associated fibroblasts (CAFs) was generated to determine whether CAFs provide niche factors essential for differentiated PDAC. PDOs were subtyped based on niche factor dependency, and the therapeutic responses for each subtype were compared. Results: The expression profiles of PDOs differed depending on the differentiation grade. Consistent with the distinct profiles, well differentiated types showed high niche dependency, while poorly differentiated types showed low niche dependency. The three-dimensional co-culture model revealed that well differentiated PDOs were strongly dependent on CAFs for growth, and moderately differentiated PDOs showed plasticity to change morphology depending on CAFs. Differentiated PDOs upregulated the expression of mevalonate pathway-related genes correlated with the niche dependency and were more sensitive to simvastatin than poorly differentiated PDOs. Conclusions: Our findings suggest that CAFs maintain the differentiated PDAC phenotype through secreting niche factors and induce distinct drug responses. These results may lead to the development of novel subtype-based therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Liver metastases (LMs) are common in advanced pancreatic neuroendocrine tumor (PNET) patients. Currently, the benefit of primary tumor resection (PTR) in the setting of PNET patients with liver metastases is still controversial in several guidelines. Methods: Data were extracted from the Surveillance, Epidemiology and End Results (SEER) database to evaluate this issue. The main index of interest in our study was overall survival time. Results: Information on 536 PNET patients with liver metastases from the SEER database was identified. A total of 214 patients (PTR group) received primary tumor resection, and more than half of them (132 patients) had synchronous LM resection. The other 322 PNET patients (non-PTR group) with liver metastases did not receive primary tumor resection. A significant survival benefit was gained from PTR when compared with non-PTR patients, both in OS (72.93 ± 2.7 vs. 36.80 ± 2.22 months) and 3- or 5-year survival rates (75.1% vs. 28.9% and 67.9% vs. 22.3%, respectively). No difference was found between PTR alone and PTR with synchronous LM resection. From univariate and multivariate analyses, younger age (<65 years) and good or moderate tumor differentiation may be more important when considering primary tumor resection. However, we found that all grades of tumor differentiation could result in a better overall survival time after primary tumor resection. Conclusion: Our study suggested that primary tumor resection in pancreatic neuroendocrine patients with liver metastases could result in a longer survival time. Primary tumor resection with synchronous liver metastasis resection was not related to a better survival benefit. This treatment strategy may routinely be taken into consideration in these patients. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the main cancer types due to its persistently high incidence and mortality, yet a simple and effective prognostic model is still lacking. This study aimed to identify independent prognostic genes related to the heterogeneity of lung adenocarcinoma (LUAD), generate a prognostic risk score model, and construct a nomogram in combination with other pathological characteristics to predict patients’ overall survival (OS). A significant amount of data pertaining to single-cell RNA sequencing (scRNA-seq), RNA sequencing (RNA-seq), and somatic mutation were used for data mining. After statistical analyses, a risk scoring model was established based on eight independent prognostic genes, and the OS of high-risk patients was significantly lower than that of low-risk patients. Interestingly, high-risk patients were more sensitive and effective to immune checkpoint blocking therapy. In addition, it was noteworthy that CCL20 not only affected prognosis and differentiation of LUAD but also led to poor histologic grade of tumor cells. Ultimately, combining risk score, clinicopathological information, and CCL20 mutation status, a nomogram with good predictive performance and high accuracy was established. In short, our research established a prognostic model that could be used to guide clinical practice based on the constantly updated big multi-omics data. Finally, this analysis revealed that CCL20 may become a potential therapeutic target for LUAD.

BackgroundLiver metastases (LMs) are common in advanced pancreatic neuroendocrine tumor (PNET) patients. Currently, the benefit of primary tumor resection (PTR) in the setting of PNET patients with liver metastases is still controversial in several guidelines.MethodsData were extracted from the Surveillance, Epidemiology and End Results (SEER) database to evaluate this issue. The main index of interest in our study was overall survival time.ResultsInformation on 536 PNET patients with liver metastases from the SEER database was identified. A total of 214 patients (PTR group) received primary tumor resection, and more than half of them (132 patients) had synchronous LM resection. The other 322 PNET patients (non-PTR group) with liver metastases did not receive primary tumor resection. A significant survival benefit was gained from PTR when compared with non-PTR patients, both in OS (72.93 ± 2.7 vs. 36.80 ± 2.22 months) and 3- or 5-year survival rates (75.1% vs. 28.9% and 67.9% vs. 22.3%, respectively). No difference was found between PTR alone and PTR with synchronous LM resection. From univariate and multivariate analyses, younger age (

Abstract Background The principle of loss of iodine uptake and increased glucose metabolism according to dedifferentiation of thyroid cancer is clinically assessed by imaging. Though these biological properties are widely applied to appropriate iodine therapy, the understanding of the genomic background of this principle is still lacking. We investigated the association between glucose metabolism and differentiation in advanced thyroid cancer as well as papillary thyroid cancer (PTC). Methods We used RNA sequencing of 505 patients with PTC obtained from the Cancer Genome Archives and microarray data of poorly-differentiated and anaplastic thyroid cancer (PDTC/ATC). The signatures of GLUT and glycolysis were estimated to assess glucose metabolic profiles. The glucose metabolic profiles were associated with tumor differentiation score (TDS) and BRAFV600E mutation status. In addition, survival analysis of glucose metabolic profiles was performed for predicting recurrence-free survival. Results In PTC, the glycolysis signature was positively correlated with TDS, while the GLUT signature was inversely correlated with TDS. These correlations were significantly stronger in the BRAFV600E negative group than the positive group. Meanwhile, both GLUT and glycolysis signatures were negatively correlated with TDS in advanced thyroid cancer. The high glycolysis signature was significantly associated with poor prognosis in PTC in spite of high TDS. The glucose metabolic profiles are intricately associated with tumor differentiation in PTC and PDTC/ATC. Conclusions As glycolysis was an independent prognostic marker, we suggest that the glucose metabolism features of thyroid cancer could be another biological progression marker different from differentiation and provide clinical implications for risk stratification. Trial registration Not applicable.

Uterine Corpus Endometrial Carcinoma (UCEC) is one of the most common malignancies of the female genital tract and there remains a major public health problem. Although significant progress has been made in explaining the progression of UCEC, it is still warranted that molecular mechanisms underlying the tumorigenesis of UCEC are to be elucidated. The aim of the current study was to investigate key modules and hub genes related to UCEC pathogenesis, and to explore potential biomarkers and therapeutic targets for UCEC. The RNA-seq dataset and corresponding clinical information for UCEC patients were obtained from the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were screened between 23 paired UCEC tissues and adjacent non-cancerous tissues. Subsequently, the co-expression network of DEGs was determined via weighted gene co-expression network analysis (WGCNA). The Blue and Brown modules were identified to be significantly positively associated with neoplasm histologic grade. The highly connected genes of the two modules were then investigated as potential key factors related to tumor differentiation. Additionally, a protein-protein interaction (PPI) network for all genes in the two modules was constructed to obtain key modules and nodes. 10 genes were identified by both WGCNA and PPI analyses, and it was shown by Kaplan-Meier curve analysis that 6 out of the 10 genes were significantly negatively related to the 5-year overall survival (OS) in patients (AURKA, BUB1, CDCA8, DLGAP5, KIF2C, TPX2). Besides, according to the DEGs from the two modules, lncRNA-miRNA-mRNA and lncRNA-TF-mRNA networks were constructed to explore the molecular mechanism of UCEC-related lncRNAs. 3 lncRNAs were identified as being significantly negatively related to the 5-year OS (AC015849.16, DUXAP8 and DGCR5), with higher expression in UCEC tissues compared to non-tumor tissues. Finally, quantitative Real-time PCR was applied to validate the expression patterns of hub genes. Cell proliferation and colony formation assays, as well as cell cycle distribution and apoptosis analysis, were performed to test the effects of representative hub genes. Altogether, this study not only promotes our understanding of the molecular mechanisms for the pathogenesis of UCEC but also identifies several promising biomarkers in UCEC development, providing potential therapeutic targets for UCEC. [ABSTRACT FROM AUTHOR]

Methods: We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). Results: Between 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three‐level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5‐year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p < 0.001), distant metastases (DM, 6%/18%/40%, p < 0.001), disease‐free survival (DFS, 78%/63%/46%, p < 0.001), disease‐specific survival (DSS, 85%/71%/49%, p < 0.001), and overall survival (OS, 68%/55%/39%, p < 0.001). Multivariable analysis identified the following variables as independent prognosticators for 5‐year outcomes: ENE (LC/NC/DM/DFS/DSS/OS), poorly differentiated tumors (NC/DM/DFS/DSS/OS), positive margins (LC/DFS), lymphatic invasion (DFS/DSS/OS), perineural invasion (DM), and age ≥65 years (OS). Conclusions: In addition to ENE, poor tumor differentiation was identified as the second most relevant adverse RF for patients with pT3–4 OCSCC. We suggest that the NCCN guidelines should include poor tumor differentiation as an adverse RF to refine and tailor clinical management. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). Methods: A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. Results: In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07–1.59), 1.07 (95% CI 0.89–1.28), 1.31 (95% CI 1.06–1.62), and 1.81 (95% CI 1.03–3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69–2.14), 1.33 (95% CI 1.02–1.73), and 1.58 (95% CI 1.04–2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46–1.57), 1.34 (95% CI 1.01–1.8), and 1.57 (95% CI 1.03–2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83–4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98–5.54) in those with tumors measuring ≥5 cm. Conclusions: Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear.Methods: We performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan-Meier and Cox's proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination.Results: Immunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified age at diagnosis, tumor site, HER1, HER3 and age at diagnosis, tumor stage, HER1, HER3, as covariates significantly associated with RFS and OS, respectively. Bootstrapping verified the good fitness of these models for predicting survivals and the optimism-corrected C-indices were 0.76 and 0.77 for RFS and OS, respectively.Conclusions: Nuclear HER3 expression was strongly associated with favourable prognosis and allows to improve the prognostic stratification of patients with HER1 positive advanced LSCC carcinoma. [ABSTRACT FROM AUTHOR]

Loss of cell differentiation is a hallmark for the progression of oral squamous cell carcinoma (OSCC). Archival Formalin-Fixed Paraffin-Embedded (FFPE) tissues constitute a valuable resource for studying the differentiation of OSCC and can offer valuable insights into the process of tumor progression. In the current study, we performed LC–MS/MS-based quantitative proteomics of FFPE specimens from pathologically-confirmed well-differentiated, moderately-differentiated, and poorly-differentiated OSCC cases. The data were analyzed in four technical replicates, resulting in the identification of 2376 proteins. Of these, 141 and 109 were differentially expressed in moderately-differentiated and poorly differentiated OSCC cases, respectively, compared to well-differentiated OSCC. The data revealed significant metabolic reprogramming with respect to lipid metabolism and glycolysis with proteins belonging to both these processes downregulated in moderately-differentiated OSCC when compared to well-differentiated OSCC. Signaling pathway analysis indicated the alteration of extracellular matrix organization, muscle contraction, and glucose metabolism pathways across tumor grades. The extracellular matrix organization pathway was upregulated in moderately-differentiated OSCC and downregulated in poorly differentiated OSCC, compared to well-differentiated OSCC. PADI4, an epigenetic enzyme transcriptional regulator, and its transcriptional target HIST1H1B were both found to be upregulated in moderately differentiated and poorly differentiated OSCC, indicating epigenetic events underlying tumor differentiation. In conclusion, the findings support the advantage of using high-resolution mass spectrometry-based FFPE archival blocks for clinical and translational research. The candidate signaling pathways identified in the study could be used to develop potential therapeutic targets for OSCC. [ABSTRACT FROM AUTHOR]

Uterine Corpus Endometrial Carcinoma (UCEC) is one of the most common malignancies of the female genital tract and there remains a major public health problem. Although significant progress has been made in explaining the progression of UCEC, it is still warranted that molecular mechanisms underlying the tumorigenesis of UCEC are to be elucidated. The aim of the current study was to investigate key modules and hub genes related to UCEC pathogenesis, and to explore potential biomarkers and therapeutic targets for UCEC. The RNA-seq dataset and corresponding clinical information for UCEC patients were obtained from the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were screened between 23 paired UCEC tissues and adjacent non-cancerous tissues. Subsequently, the co-expression network of DEGs was determined via weighted gene co-expression network analysis (WGCNA). The Blue and Brown modules were identified to be significantly positively associated with neoplasm histologic grade. The highly connected genes of the two modules were then investigated as potential key factors related to tumor differentiation. Additionally, a protein-protein interaction (PPI) network for all genes in the two modules was constructed to obtain key modules and nodes. 10 genes were identified by both WGCNA and PPI analyses, and it was shown by Kaplan-Meier curve analysis that 6 out of the 10 genes were significantly negatively related to the 5-year overall survival (OS) in patients (AURKA, BUB1, CDCA8, DLGAP5, KIF2C, TPX2). Besides, according to the DEGs from the two modules, lncRNA-miRNA-mRNA and lncRNA-TF-mRNA networks were constructed to explore the molecular mechanism of UCEC-related lncRNAs. 3 lncRNAs were identified as being significantly negatively related to the 5-year OS (AC015849.16, DUXAP8 and DGCR5), with higher expression in UCEC tissues compared to non-tumor tissues. Finally, quantitative Real-time PCR was applied to validate the expression patterns of hub genes. Cell proliferation and colony formation assays, as well as cell cycle distribution and apoptosis analysis, were performed to test the effects of representative hub genes. Altogether, this study not only promotes our understanding of the molecular mechanisms for the pathogenesis of UCEC but also identifies several promising biomarkers in UCEC development, providing potential therapeutic targets for UCEC.

Purpose: To investigate if quantitative contrast enhancement and iodine mapping of common brain tumor (BT) entities may correctly differentiate between tumor etiologies in standardized stereotactic CT protocols. Material and Methods: A retrospective monocentric study of 139 consecutive standardized dual-layer dual-energy CT (dlDECT) scans conducted prior to the stereotactic needle biopsy of untreated primary brain tumor lesions. Attenuation of contrast-enhancing BT was derived from polyenergetic images as well as spectral iodine density maps (IDM) and their contrast-to-noise-ratios (CNR) were determined using ROI measures in contrast-enhancing BT and healthy contralateral white matter. The measures were correlated to histopathology regarding tumor entity, isocitrate dehydrogenase (IDH) and MGMT mutation status. Results: The cohort included 52 female and 76 male patients, mean age of 59.4 (±17.1) years. Brain lymphomas showed the highest attenuation (IDM CNR 3.28 ± 1,23), significantly higher than glioblastoma (2.37 ± 1.55, p < 0.005) and metastases (1.95 ± 1.14, p < 0.02), while the differences between glioblastomas and metastases were not significant. These strongly enhancing lesions differed from oligodendroglioma and astrocytoma (Grade II and III) that showed IDM CNR in the range of 1.22–1.27 (±0.45–0.82). Conventional attenuation measurements in DLCT data performed equally or slightly superior to iodine density measurements. Conclusion: Quantitative attenuation and iodine density measurements of contrast-enhancing brain tumors are feasible imaging biomarkers for the discrimination of cerebral tumor lesions but not specifically for single tumor entities. CNR based on simple HU measurements performed equally or slightly superior to iodine quantification.

Cholangiocarcinoma (CCA) is a type of cancer with limited treatment options and a poor prognosis. Although some important genes and pathways associated with CCA have been identified, the relationship between coexpression and phenotype in CCA at the systems level remains unclear. In this study, the relationships underlying the molecular and clinical characteristics of CCA were investigated by employing weighted gene coexpression network analysis (WGCNA). The gene expression profiles and clinical features of 36 patients with CCA were analyzed to identify differentially expressed genes (DEGs). Subsequently, the coexpression of DEGs was determined by using the WGCNA method to investigate the correlations between pairs of genes. Network modules that were significantly correlated with clinical traits were identified. In total, 1478 mRNAs were found to be aberrantly expressed in CCA. Seven coexpression modules that significantly correlated with clinical characteristics were identified and assigned representative colors. Among the 7 modules, the green and blue modules were significantly related to tumor differentiation. Seventy-eight hub genes that were correlated with tumor differentiation were found in the green and blue modules. Survival analysis showed that 17 hub genes were prognostic biomarkers for CCA patients. In addition, we found five new targets (ISM1, SULT1B1, KIFC1, AURKB and CCNB1) that have not been studied in the context of CCA and verified their differential expression in CCA through experiments. Our results not only promote our understanding of the relationship between the transcriptome and clinical data in CCA but will also guide the development of targeted molecular therapy for CCA. [ABSTRACT FROM AUTHOR]

Prostate cancer incidence in young men has increased. Patients diagnosed at an earlier age are likely to have aggressive prostate cancer and treatment decisions are continuing to be weighted by patient age and life expectancy. Identification of age-associated gene-expression signatures hold great potential to augment current and future treatment modalities. To investigate age-specific tumor associated gene signatures and their potential biomarkers for disease aggressiveness, this study was designed and stratified into well and poorly differentiated tumor types of young (42–58 years) and old (66–73 years) prostate cancer patients. The differentially expressed genes related to tumor-normal differences between non-familial prostate cancer patients were identified and several genes uniquely associated with the age and tumor differentiation are markedly polarized. Overexpressed genes known to be associated with somatic genomic alterations was predominantly found in young men, such as TMPRESS2-ERG and c-MYC. On the other hand, old men have mostly down-regulated gene expressions indicating the loss of protective genes and reduced cell mediated immunity indicated by decreased HLA-A and HLA-B expression. The normalization for the benign signatures between the age groups indicates a significant age and tumor dependent heterogeneity exists among the patients with a great potential for age-specific and tumor differentiation-based therapeutic stratification of prostate cancer.

Prostate cancer incidence in young men has increased. Patients diagnosed at an earlier age are likely to have aggressive prostate cancer and treatment decisions are continuing to be weighted by patient age and life expectancy. Identification of age-associated gene-expression signatures hold great potential to augment current and future treatment modalities. To investigate age-specific tumor associated gene signatures and their potential biomarkers for disease aggressiveness, this study was designed and stratified into well and poorly differentiated tumor types of young (42–58 years) and old (66–73 years) prostate cancer patients. The differentially expressed genes related to tumor-normal differences between non-familial prostate cancer patients were identified and several genes uniquely associated with the age and tumor differentiation are markedly polarized. Overexpressed genes known to be associated with somatic genomic alterations was predominantly found in young men, such as TMPRESS2-ERG and c-MYC. On the other hand, old men have mostly down-regulated gene expressions indicating the loss of protective genes and reduced cell mediated immunity indicated by decreased HLA-A and HLA-B expression. The normalization for the benign signatures between the age groups indicates a significant age and tumor dependent heterogeneity exists among the patients with a great potential for age-specific and tumor differentiation-based therapeutic stratification of prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the predictive factors of pathologic complete response (pCR) in locally advanced rectal cancer (LARC) patients who had been treated with neoadjuvant chemoradiation (nCRT)., Methods and Materials: For this retrospective study, 53 LARC patients (37 males and 16 females; age range 25 to 79 years) were selected. Clinical characteristics, baseline mrTNM staging, MR gross tumor volumes (GTV), and pCR were evaluated. The diagnostic accuracy of GTV for predicting pCR was calculated., Results: Among 53 LARC patients, 15 patients achieved pCR (28.3%), while 38 patients achieved non-pCR. Only three (5.7%) out of 53 patients did not downstage after nCRT. GTV and tumor differentiation were the significant prognostic parameters for predicting pCR. A tumor volume threshold of 21.1 cm 3 was determined as a predictor for pCR, with a sensitivity of 84% and specificity of 47%. In addition, GTV was associated with mrN stage, circumferential resection margin (CRM) status, extramural vascular invasion (EMVI) status, and pretreatment serum CEA level., Conclusion: Tumor volume and tumor differentiation have significant predictive values in preoperative assessment of pCR among LARC patients. These findings aid clinicians to discriminate those patients who may likely benefit from preoperative regimens and to make optimal treatment plans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhong, Zeng, Zhang, You, Fu, He and Liao.)

Abstract Background Gastric cancer is common in developing regions, and we hope to find out an economical but practical prognostic indicator. It was reported that pre-treatment peripheral neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as well as differentiation status, were associated with cancer progression. Hence, we introduced a novel combined Neutrophil/platelet/lymphocyte/differentiation Score (cNPLDS) to improve the prediction value of palliative chemotherapeutic response in advanced gastric cancer. Methods According to statistical sample size estimation, 136 primary diagnosed unresectable advanced ptaients were included for a retrospective study. The follow-up end-point was progression free survival (PFS) during the first-line palliative chemotherapy. Differentiation stratified patients into well, medium and poor groups by score 1 to 3, while patients with neither elevated NLR and PLR, only one elevated, or both elevated were of the combined NLR-PLR score (cNPS) 1 to 3, respectively. The cNPLDS was calculated by multiplying the tumor differentiation score and cNPS. Results Determined by the receiver operating characteristic (ROC) curve, the optimal cut-off points for NLR and PLR were 3.04 and 223. Through univariate analysis and survival analysis, poor differentiation, high NLR, high PLR, high cNPS, and high cNPLDS respectively indicated inferior PFS during the first-line palliative chemotherapy. Patients were furhter classified into low to high risk groups by cNPLDS. Groups of elevated NLR, PLR, cNPS, and cNPLDS showed lower disease control rate. Compared to other parameters, cNPLDS significantly improved the accuracy in predicing the first-progression. Conclusions This study indicates that the novel parameter cNPLDS is superior to NLR or PLR alone, or even cNPS, in predicting the first-line chemosensitivity in advanced gastric cancer.

Background: The principle of loss of iodine uptake and increased glucose metabolism according to dedifferentiation of thyroid cancer is clinically assessed by imaging. Though these biological properties are widely applied to appropriate iodine therapy, the understanding of the genomic background of this principle is still lacking. We investigated the association between glucose metabolism and differentiation in advanced thyroid cancer as well as papillary thyroid cancer (PTC).Methods: We used RNA sequencing of 505 patients with PTC obtained from the Cancer Genome Archives and microarray data of poorly-differentiated and anaplastic thyroid cancer (PDTC/ATC). The signatures of GLUT and glycolysis were estimated to assess glucose metabolic profiles. The glucose metabolic profiles were associated with tumor differentiation score (TDS) and BRAFV600E mutation status. In addition, survival analysis of glucose metabolic profiles was performed for predicting recurrence-free survival.Results: In PTC, the glycolysis signature was positively correlated with TDS, while the GLUT signature was inversely correlated with TDS. These correlations were significantly stronger in the BRAFV600E negative group than the positive group. Meanwhile, both GLUT and glycolysis signatures were negatively correlated with TDS in advanced thyroid cancer. The high glycolysis signature was significantly associated with poor prognosis in PTC in spite of high TDS. The glucose metabolic profiles are intricately associated with tumor differentiation in PTC and PDTC/ATC.Conclusions: As glycolysis was an independent prognostic marker, we suggest that the glucose metabolism features of thyroid cancer could be another biological progression marker different from differentiation and provide clinical implications for risk stratification.Trial Registration: Not applicable. [ABSTRACT FROM AUTHOR]

Abstract Background The differentiation of pancreatic ductal adenocarcinoma (PDAC) could be associated with prognosis and may influence the choices of clinical management. No applicable methods could reliably predict the tumor differentiation preoperatively. Thus, the aim of this study was to compare the metabonomic profiling of pancreatic ductal adenocarcinoma with different differentiations and assess the feasibility of predicting tumor differentiations through metabonomic strategy based on nuclear magnetic resonance spectroscopy. Methods By implanting pancreatic cancer cell strains Panc-1, Bxpc-3 and SW1990 in nude mice in situ, we successfully established the orthotopic xenograft models of PDAC with different differentiations. The metabonomic profiling of serum from different PDAC was achieved and analyzed by using 1H nuclear magnetic resonance (NMR) spectroscopy combined with the multivariate statistical analysis. Then, the differential metabolites acquired were used for enrichment analysis of metabolic pathways to get a deep insight. Results An obvious metabonomic difference was demonstrated between all groups and the pattern recognition models were established successfully. The higher concentrations of amino acids, glycolytic and glutaminolytic participators in SW1990 and choline-contain metabolites in Panc-1 relative to other PDAC cells were demonstrated, which may be served as potential indicators for tumor differentiation. The metabolic pathways and differential metabolites identified in current study may be associated with specific pathways such as serine-glycine-one-carbon and glutaminolytic pathways, which can regulate tumorous proliferation and epigenetic regulation. Conclusion The NMR-based metabonomic strategy may be served as a non-invasive detection method for predicting tumor differentiation preoperatively.

Flotillin 1 (FLOT1) is increasingly implicated in various types of cancer, and has been reported to influence tumorigenesis and cancer progression, leading to poor prognosis for survival time; however, its expression in colorectal cancer (CRC) and its influence on various clinicopathological parameters of this disease remain unknown. In the present study, FLOT1 expression and its effect on different clinicopathological parameters were assessed immunohistochemically and histologically in 81 CRC and 81 non-tumorous colon tissue samples. The immunohistochemical staining was scored semi-quantitatively. The association of FLOT1 expression with various parameters and its effect on overall survival time was also assessed. FLOT1 was upregulated in the CRC tissue, with increased expression in the right colon tissue samples compared with those of left colon. Increased FLOT1 expression in CRC tissue samples was associated with tumor volume, differentiation, tumor grade and poor overall survival time. In the right colon tissue samples in particular, there was a notable association with tumor volume and grade, indicating its effect on proliferation and tumor stage at this site. A multivariate Cox regression hazard analysis revealed that only tumor grade and differentiation were the independent predictors of overall survival time in patients with CRC. Together, the results of the present study suggest that FLOT1 serves important functions in the proliferation and progression of CRC, contributes to decreased survival time, and may serve as a novel therapeutic target for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Poorly differentiated non-small cell lung cancer (NSCLC) indicated a poor prognosis and well-differentiated NSCLC indicates a noninvasive nature and good prognosis. The purpose of this study was to build and validate a radiomics signature to predict the degree of tumor differentiation (DTD) for patients with NSCLC.Materials and Methods: A total of 487 patients with pathologically diagnosed NSCLC were retrospectively included in our study. Five hundred ninety-one radiomics features were extracted from each tumor from the contrast-enhanced computed tomography images. A minimum redundancy maximum relevance algorithm and a logistic regression model were used for dimension reduction, feature selection, and radiomics signature building. The performance of the radiomics signature was assessed using receiver operating characteristic analysis, and the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were calculated to quantify the association between a signature and DTD. An independent validation set contained 184 consecutive patients with NSCLC.Results: A nine-radiomics-feature-based signature was built and it could differentiate low and high DTDs in the training set (AUC = 0.763, sensitivity = 0.750, specificity = 0.665, and accuracy = 0.687), and the radiomics signature had good discrimination performance in the validation set (AUC = 0.782, sensitivity = 0.608, specificity = 0.752, and accuracy = 0.712).Conclusions: A radiomics signature based on contrast-enhanced computed tomography imaging is a potentially useful imaging biomarker for differentiating low from high DTD in patients with NSCLC. [ABSTRACT FROM AUTHOR]

Dual-energy computed tomography (DECT) can estimate tissue vascularity and perfusion via iodine quantification. The aim of this systematic review was to outline current and emerging clinical applications of iodine quantification within the gastrointestinal tract using DECT. The search was conducted with three databases: EMBASE, Pubmed and The Cochrane Library. This identified 449 studies after duplicate removal. From a total of 570 selected studies, 30 studies were enrolled for the systematic review. The studies were categorized into four main topics: gastric tumors (12 studies), colorectal tumors (8 studies), Crohn’s disease (4 studies) and miscellaneous applications (6 studies). Findings included a significant difference in iodine concentration (IC) measurements in perigastric fat between T1–3 vs. T4 stage gastric cancer, poorly and well differentiated gastric and colorectal cancer, responders vs. non-responders following chemo- or chemoradiotherapy treatment among cancer patients, and a positive correlation between IC and Crohn’s disease activity. In conclusion, iodine quantification with DECT may be used preoperatively in cancer imaging as well as for monitoring treatment response. Future studies are warranted to evaluate the capabilities and limitations of DECT in splanchnic flow.

Notch deregulation has been reported in various types of cancers, including Oral squamous cell carcinomas (OSCCs). The role of Notch1 signaling in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, NOTCH1 was aberrantly expressed in human oral cancer tissues compared with that in normal marginal tissues and was associated with poor prognosis. The positive Notch 1 expression was significantly associated with poor tumor differentiation status. Kaplan-Meier survival curves revealed that elevated cytoplasmic NOTCH1 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate COX proportional hazard models revealed that T N status, AJCC stage histological grade were independent prognostic factors for survival. Our result clearly demonstrates the oncogenic role of Notch1 in oral cancer and Notch1 may be a useful biomarker to target oral cancer patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with high metastatic potential. Clinical observations suggest that there is disease heterogeneity among patients with different sites of distant metastases, yielding distinct clinical outcomes. Herein, we investigate the impact of clinical and pathological parameters on recurrence patterns and compare survival outcomes for patients with a first site of recurrence in the liver versus lung from PDAC following original curative surgical resection.Methods: Using the Memorial Sloan Kettering Cancer Center ICD billing codes and tumor registry database over a 10 years period (January 2004-December 2014), we identified PDAC patients who underwent resection and subsequently presented with either liver or lung recurrence. Time from relapse to death (TRD) was calculated from date of recurrence to date of death. Using the Kaplan-Meier method, TRD was estimated and compared by recurrence site using log-rank test.Results: The median overall follow-up was 37.3 months among survivors in the entire cohort. Median TRD in this cohort was 10.7 months (95%CI: 8.9-14.6 months). Patients with first site of lung recurrence had a more favorable outcome compared to patients who recurred with liver metastasis as the first site of recurrence (median TRD of 15 versus 9 months respectively, P = 0.02). Moderate to poorly or poor differentiation was associated more often with liver than lung recurrence (40% vs 21% respectively, P = 0.047). A trend to increased lymph node metastasis in the lung recurrence cohort was observed.Conclusion: PDAC patients who recur with a first site of lung metastasis have an improved clinical outcome compared to patients with first site of liver recurrence. Our data suggests there may be epidemiologic and pathologic determinants related to patterns of recurrence in PDAC. [ABSTRACT FROM AUTHOR]

Brain tumors are the most common malignant neurologic tumors with the highest mortality and disability rate. Because of the delicate structure of the brain, the clinical use of several commonly used biopsy diagnosis is limited for brain tumors. Radiomics is an emerging technique for noninvasive diagnosis based on quantitative medical image analyses. However, current radiomics techniques are not standardized regarding feature extraction, feature selection, and decision making. In this paper, we propose a sparse representation-based radiomics (SRR) system for the diagnosis of brain tumors. First, we developed a dictionary learning- and sparse representation-based feature extraction method that exploits the statistical characteristics of the lesion area, leading to fine and more effective feature extraction compared with the traditional explicitly calculation-based methods. Then, we set up an iterative sparse representation method to solve the redundancy problem of the extracted features. Finally, we proposed a novel multi-feature collaborative sparse representation classification framework that introduces a new coefficient of regularization term to combine features from multi-modal images at the sparse representation coefficient level. Two clinical problems were used to validate the performance and usefulness of the proposed SRR system. One was the differential diagnosis between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM), and the other was isocitrate dehydrogenase 1 estimation for gliomas. The SRR system had superior PCNSL and GBM differentiation performance compared with some advanced imaging techniques and yielded 11% better performance for estimating IDH1 compared with the traditional radiomics methods. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Gastroenteropancreatic neuroendocrine neoplasms (GEP‐NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification. The purpose of our study was to evaluate the prognostic impact of histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories, and explore additional Ki‐67 cutoff values in GEP‐NENs. Subjects, Materials, and Methods: A total of 2,813 patients from the Spanish National Tumor Registry (RGETNE) were analyzed. Cases were classified by histological differentiation as NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine carcinomas [poorly differentiated]), and by Ki‐67 index as G1 (Ki‐67 <2%), G2 (Ki‐67 3%–20%), or G3 (Ki‐67 >20%). Patients were stratified into five cohorts: NET‐G1, NET‐G2, NET‐G3, NEC‐G2, and NEC‐G3. Results: Five‐year survival was 72%. Age, gender, tumor site, grade, differentiation, and stage were all independent prognostic factors for survival. Further subdivision of the WHO 2010 grading improved prognostic stratification, both within G2 (5‐year survival: 81% [Ki‐67 3%–5%], 72% [Ki‐67 6%–10%], 52% [Ki‐67 11%–20%]) and G3 NENs (5‐year survival: 35% [Ki‐67 21%–50%], 22% [Ki‐67 51%–100%]). Five‐year survival was significantly greater for NET‐G2 versus NEC‐G2 (75.5% vs. 58.2%) and NET‐G3 versus NEC‐G3 (43.7% vs. 25.4%). Conclusion: Substantial clinical heterogeneity is observed within G2 and G3 GEP‐NENs. The WHO 2010 classification can be improved by including the additive effect of histological differentiation and the proliferation index. Implications for Practice: Gastroenteropancreatic neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly stratified by the World Health Organization (WHO) 2010 classification into three subgroups based on proliferation index. Real‐world data from 2,813 patients of the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further subdivision of grading substantially improves prognostic stratification of these patients and may help individualize therapy. This combined, additive effect shall be considered in future classifications of neuroendocrine tumors and incorporated for stratification purposes in clinical trials. [ABSTRACT FROM AUTHOR]